Small molecule control of pre-mRNA splicing
Small molecule control of pre-mRNA splicing
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DOI：
10.1261/rna.7229705
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发表时间：
2005-03-01
期刊：
影响因子：
4.5
通讯作者：
Graveley, BR
中科院分区：
文献类型：
--
作者：
Graveley, BR
SR蛋白通过与外显子序列结合来调节可变剪接，其中，通过富含精氨酸/丝氨酸的剪接激活结构域，它们增强剪接体与相邻剪接位点的结合。这里，描述了一种系统，其中使用小分子雷帕霉素的无毒衍生物来控制体外前体mRNA剪接。这涉及雷帕霉素依赖性募集位于一种蛋白质上的剪接激活结构域到与前体mRNA结合的第二种蛋白质。这些结果为探索小分子通过调控前体mRNA剪接调控体内基因表达提供了新的途径。
SR proteins regulate alternative splicing by binding to exonic sequences where, via an arginine/serine-rich splicing activation domain, they enhance the binding of the spliceosome to the adjacent splice sites. Here, a system is described in which a nontoxic derivative of the small molecule rapamycin is used to control pre-mRNA splicing in vitro. This involves the rapamycin-dependent recruitment of a splicing activation domain located on one protein to a second protein bound to the pre-mRNA. These results provide a new approach to explore for regulating gene expression in vivo with small molecules by controlling pre-mRNA splicing.